Abstract
BackgroundThere has been a rapid increase in the brain size relative to body size during mammalian evolutionary history. In particular, the enlarged and globular brain is the most distinctive anatomical feature of modern humans that set us apart from other extinct and extant primate species. Genetic basis of large brain size in modern humans has largely remained enigmatic. Genes associated with the pathological reduction of brain size (primary microcephaly-MCPH) have the characteristics and functions to be considered ideal candidates to unravel the genetic basis of evolutionary enlargement of human brain size. For instance, the brain size of microcephaly patients is similar to the brain size of Pan troglodyte and the very early hominids like the Sahelanthropus tchadensis and Australopithecus afarensis.ResultsThe present study investigates the molecular evolutionary history of subset of autosomal recessive primary microcephaly (MCPH) genes; CEP135, ZNF335, PHC1, SASS6, CDK6, MFSD2A, CIT, and KIF14 across 48 mammalian species. Codon based substitutions site analysis indicated that ZNF335, SASS6, CIT, and KIF14 have experienced positive selection in eutherian evolutionary history. Estimation of divergent selection pressure revealed that almost all of the MCPH genes analyzed in the present study have maintained their functions throughout the history of placental mammals. Contrary to our expectations, human-specific adoptive evolution was not detected for any of the MCPH genes analyzed in the present study.ConclusionBased on these data it can be inferred that protein-coding sequence of MCPH genes might not be the sole determinant of increase in relative brain size during primate evolutionary history.
Highlights
There has been a rapid increase in the brain size relative to body size during mammalian evolutionary history
Molecular evolutionary analysis of MCPH genes In order to investigate the genetic basis of the evolutionary expansion of human brain, eight newly identified MCPH genes (CEP135, ZNF335, PHC1, CDK6, SASS6, MFSD2A, CIT, and KIF14) were considered as candidates for evolutionary analysis
Signature of pervasive positive selection in MCPH genes In order to examine whether the pervasive positive selection has operated on selected subset of MCPH genes (CEP135, ZNF335, PHC1, CDK6, SASS6, MFSD2A, CIT, and KIF14), three pairs of site models (M1 & M2, M7 & M8, and M8a & M8) based on codon substitutions were used
Summary
There has been a rapid increase in the brain size relative to body size during mammalian evolutionary history. Genes associated with the pathological reduction of brain size (primary microcephaly-MCPH) have the characteristics and functions to be considered ideal candidates to unravel the genetic basis of evolutionary enlargement of human brain size. The brain size of microcephaly patients is similar to the brain size of Pan troglodyte and the very early hominids like the Sahelanthropus tchadensis and Australopithecus afarensis. The modern human brain is approximately three-fold larger in size than that of our closest extant relative, the chimpanzee, and extinct early hominids. Many previously reported molecular evolutionary investigations have implicated MCPH genes (like ASPM and CDK5RAP2) in the expansion and reduction of brain size during primate history [30, 31]
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